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Biomedical subjects

J A Izatt

Publications and source records attributed to J A Izatt.

At least 19 recordsLinked to original sources

Electrostatic micromachine scanning mirror for optical coherence tomography.

Compact electrostatic micromirror structures for use in the scanning arm of an optical coherence tomography (OCT) system are described. These devices consist of millimeter-scale mirrors resting upon micrometer-scale polyimide hinges that are tilted by a linear micromachine actuator, the integrated force array (IFA). The IFA is a network of deformable capacitor cells that electrostatically contract with an applied voltage. The support structures, hinges, and actuators are fabricated by photolithography from polyimide-upon-silicon wafers. These devices were inserted into the scanning arm of an experimental OCT imaging system to produce in vitro and in vivo images at frame rates of 4 to 8 Hz.

Electricity↗

Free of speckle ultrasound images of small tissue structures.

By using the Born approximation deconvolved inverse scattering method instead of the traditional pulse-echo method for analyzing ultrasound pulse reflections from plastic phantoms and soft tissue specimens, improvement in image resolution is shown to be possible provided these targets are fair approximations to layered media. These images are free of speckle and are more vivid than the usual pulse-echo images.

Acoustics↗

Real-time optical coherence tomography of the anterior segment at 1310 nm.

BACKGROUND: Recent advances in high-speed scanning technology have enabled a new generation of optical coherence tomographic (OCT) systems to perform imaging at video rate. Here, a handheld OCT probe capable of imaging the anterior segment of the eye at high frame rates is demonstrated for the first time. OBJECTIVE: To demonstrate real-time OCT imaging of anterior segment structures. DESIGN: Survey of anterior segment structures in normal human subjects. SETTING: Laboratory. MAIN OUTCOME MEASURES: Achieving real-time imaging of the anterior segment, satisfactory image quality, and convenience of a handheld probe. RESULTS: Optical coherence tomographic imaging of the anterior segment of the eyes of human subjects was performed using 1310-nm wavelength light with an image rate of 8 frames per second. Imaging trials demonstrated clear resolution of corneal epithelium and stroma, sclerocorneal junction, sclera, iris pigment epithelium and stroma, and anterior lens capsule. The anterior chamber angle was clearly visualized. Limited imaging of the ciliary body was performed. Real-time imaging of pupillary constriction in response to light stimulus was also performed. CONCLUSION: High-speed OCT at 1310-nm wavelength is a potentially useful technique for noninvasive assessment of anterior segment structures. CLINICAL RELEVANCE: Our results suggest that real-time OCT has potential applications in glaucoma evaluation and refractive surgery.

Anterior Chamber↗

High-resolution endoscopic imaging of the GI tract: a comparative study of optical coherence tomography versus high-frequency catheter probe EUS.

BACKGROUND: Both optical coherence tomography (OCT) and catheter probe EUS (CPEUS) are candidates for high-resolution imaging of the GI wall, but their potential roles in this clinical context have not been investigated. METHODS: OCT and CPEUS were used to image normal-appearing portions of the GI tract at the same sites. CPEUS was performed with a 20-MHz or a new 30-MHz catheter probe. RESULTS: Forty-four histologically confirmed normal sites in 27 patients were evaluated. With OCT, mucosa and muscularis mucosa were clearly seen at all sites. Except for stomach, OCT demonstrated the submucosa in all sites. OCT penetration ranged from 0.7 to 0.9 mm. Microscopic structures such as esophageal glands, intestinal villi, colonic crypts, and blood vessels were easily identified. CPEUS penetration ranged from 10 mm to 20 mm, and 5 to 7 distinct layers were discernible. However, both mucosa and submucosa were seen as thin layers without microscopic detail. CONCLUSION: OCT resolution is superior to high-frequency CPEUS, but depth of penetration is limited to mucosa and submucosa. OCT images the major structural components of the mucosa and submucosa whereas CPEUS does not. Potentially, OCT and high-frequency CPEUS may be complementary for clinical imaging.

Endoscopy, Gastrointestinal↗

Photothermal coagulation of blood vessels: a comparison of high-speed optical coherence tomography and numerical modelling.

Optical-thermal models that can accurately predict temperature rise and damage in blood vessels and surrounding tissue may be used to improve the treatment of vascular disorders. Verification of these models has been hampered by the lack of time- and depth-resolved experimental data. In this preliminary study, an optical coherence tomography system operating at 4-30 frames per second was used to visualize laser irradiation of cutaneous (hamster dorsal skin flap) blood vessels. An argon laser was utilized with the following parameters: pulse duration 0.1-2.0 s, spot size 0.1-1.0 mm, power 100-400 mW. Video microscopy images were obtained before and after irradiations, and optical-thermal modelling was performed on two irradiation cases. Time-resolved optical coherence tomography and still images were compared with predictions of temperature rise and damage using Monte Carlo and finite difference techniques. In general, predicted damage agreed with the actual blood vessel and surrounding tissue coagulation seen in images. However, limitations of current optical-thermal models were identified, such as the inability to model the dynamic changes in blood vessel diameter that were seen in the optical coherence tomography images.

Animals↗

High-resolution endoscopic imaging of the GI tract using optical coherence tomography.

BACKGROUND: Optical coherence tomography (OCT) has demonstrated the microscopic structure of the gastrointestinal (GI) tract mucosa and submucosa in vitro. We evaluated a prototype OCT system and assessed the feasibility of OCT in the human GI tract. METHODS: The 2.4 mm diameter prototype OCT probe, inserted through an endoscope, provides a 360-degree radial scan. Images (6.7 frames/sec) are displayed on a television monitor. Tissue contact is not required. In patients undergoing elective endoscopy, OCT images were obtained of normal mucosa (confirmed by biopsy). RESULTS: Seventy-two sites were imaged (38 patients): esophagus (21), stomach (12), duodenum (11), terminal ileum (4), colon (15), and rectum (9). Varying the distance between the probe and the mucosal surface produced images of the GI wall of varying depth. When held about 1 mm above the mucosal surface, the images consisted of mucosal structures such as colonic crypts, gastric pits, and duodenal villi. With the probe held against the wall, the OCT image comprised several layers interpreted as mucosa, muscularis mucosae, and submucosa. Structures including blood vessels were evident within the submucosa. A probe with a 0.5 mm working distance to the focal point provided the best images. Reducing the frame rate to 4.0 per second facilitated image interpretation. CONCLUSIONS: OCT is feasible in the human GI tract and provides interpretable high-resolution images of mucosa and submucosa.

Adult↗

Quantitative analysis of Pc 4 localization in mouse lymphoma (LY-R) cells via double-label confocal fluorescence microscopy.

Photodynamic therapy (PDT) is a novel cancer therapy that uses light-activated drugs (photosensitizers) to destroy tumor tissue. Reactive oxygen species produced during PDT are thought to cause the destruction of tumor tissue. However, the precise mechanism of PDT is not completely understood. To provide insight into the in vitro mechanisms of PDT, we studied the subcellular localization of the photosensitizer HOSiPcOSi(CH3)2-(CH2)3N(CH3)2 (Pc 4) in mouse lymphoma (LY-R) cells using double-label confocal fluorescence microscopy. This technique allowed us to observe the relative distributions of Pc 4 and an organelle-specific dye within the same cell via two, spectrally distinct, fluorescence images. To quantify the localization of Pc 4 within different organelles, linear correlation coefficients from the fluorescence data of Pc 4 and the organelle-specific dyes were calculated. Using this measurement, the subcellular spatial distributions of Pc 4 could be successfully monitored over an 18 h period. At early times (0-1 h) after introduction of Pc 4 to LY-R cells, the dye was found in the mitochondria, lysosomes and Golgi apparatus, as well as other cytoplasmic membranes, but not in the plasma membrane or the nucleus. Over the next 2 h, there was some loss of Pc 4 from the lysosomes as shown by the correlation coefficients. After an additional incubation period of 2 h Pc 4 slowly increased its accumulation in the lysosomes. The highest correlation coefficient (0.65) was for Pc 4 and BODIPY-FL C5 ceramide, which targets the Golgi apparatus, and also binds to other cytoplasmic membranes. The correlation coefficient was also high (0.60) for Pc 4 and a mitochondria-targeting dye (Mitotracker Green FM). Both of these correlation coefficients were higher than that for Pc 4 with the lysosome-targeting dye (Lysotracker Green DND-26). The results suggest that Pc 4 binds preferentially and strongly to mitochondria and Golgi complexes.

Animals↗

Quantitative laser scanning confocal autofluorescence microscopy of normal, premalignant, and malignant colonic tissues.

Laser scanning confocal autofluorescence microscopy (LSCAM) using 351- to 364-nm excitation light was used to quantitatively compare fluorescent spectral emission of unstained, frozen histological sections of normal, premalignant, and malignant colonic tissues. To identify the spatial origins of fluorescent signals accurately, the same frozen section slides used for microscopy were fixed and histochemically stained immediately following LSCAM imaging. Tissue fluorescence emission was quantified in terms of the intrinsic fluorescence coefficient beta (lambda), defined as the fluorescence power per unit tissue volume per unit wavelength (centered at lambda) divided by the incident light irradiance. Over all emission wavelengths, colonic tissues emitted autofluorescence ranging from beta (lambda) approximately 10(-1.5) to 10(-3.0) cm-1. In the 530- to 610-nm spectral region, markedly increased autofluorescence (beta up to 10(-2.5)) was observed in the dysplastic cells of adenomatous polyps, as compared to normal epithelial cells. Compared to adenomatous polyps, decreased dysplastic cell autofluorescence was observed in adenocarcinoma. The brightest fluorescence in the lamina propria, which was attributed to eosinophils (beta approximately 10(-2.5)) in previous studies, was also observed in other granular structures (beta up to 10(-1.4)). LSCAM reveals quantitative significant differences in fluorescence emission between normal and diseased colonic tissues.

Adenocarcinoma↗

Three-dimensional reconstruction of blood vessels from in vivo color Doppler optical coherence tomography images.

PURPOSE: Current laser treatment for vascular disorders such as port wine stains can have incomplete or unacceptable results. A customized treatment strategy based on knowledge of the patient's blood vessel structure may effect an improved clinical outcome. PROCEDURE: We tested the feasibility of using color Doppler optical coherence tomography (OCT) and image processing techniques to locate, measure and reconstruct cutaneous blood vessels in rat and hamster skin. OCT is a recent, potentially noninvasive technique for imaging subsurface tissue structures with micrometer scale resolution. RESULTS: Blood vessels were identified in a series of cross-sectional images, then a three-dimensional reconstruction was made. Parameters that can affect optimum laser treatment parameters, such as average blood vessel depth and luminal diameter, were found from the images. CONCLUSION: This study shows that color Doppler OCT is a potential tool for improving laser treatment of vascular disorders.

Animals↗

High-resolution cross-sectional imaging of the gastrointestinal tract using optical coherence tomography: preliminary results.

BACKGROUND: Optical coherence tomography (OCT) is a novel technique for noninvasive cross-sectional imaging with high spatial resolution (10 to 20 microm). OCT is similar to B-mode ultrasound except that it uses infrared light rather than ultrasound. We studied OCT imaging of the gastrointestinal (GI) tract in vitro to analyze the potential of this technique for endoscopic applications. METHODS: Human gastrointestinal tissues harvested from surgical resection and autopsy specimens were used. Specimens were imaged within 5 hours of resection or snap frozen in liquid nitrogen. After imaging, OCT scan locations were carefully marked using dye microinjections, fixed, and prepared for routine histologic processing. OCT images were then compared and correlated with the histologic sections. RESULTS: OCT images demonstrated clear delineation of the mucosa and submucosa in most specimens. Furthermore, microscopic structures such as crypts, blood vessels, or esophageal glands in the submucosa and lymphatic nodules were observed. CONCLUSIONS: The resolution of OCT images of GI wall is sufficient to delineate the microscopic structure of the mucosa and submucosa. Potentially, OCT would allow in vivo imaging at endoscopy of the microstructure of the mucosa and submucosa. This would be particularly useful in the detection and staging of small lesions such as early stage cancers.

Anatomy, Cross-Sectional↗

Real-time frequency domain temperature and oxygen sensor with a single optical fiber.

The combined excited-state phosphorescence life-times of an alexandrite crystal and platinum tetraphenylporphyrin Pt(TPP) in a single-fiber sensor are used to monitor temperature and oxygen concentration in the physiological range from 15-45 degrees C and 0-50% O2 with precision of 0.24 degree C and 0.15% O2 and accuracy of 0.28 degree C and 0.2% O2. A 500-micron cubic alexandrite crystal bound to the distal end of a 750-micron-diameter optical fiber core and the Pt(TPP) coated circumferentially with a length of 1 cm from the end of the same fiber are excited with pulsed super-bright blue LED light. This apparatus uses a 125-kHz sampler for data acquisition and frequency domain methods for signal processing. The instrument amplifies both the dc and ac components of the photomultiplier output and band limits the signal to 20 kHz. The fundamental frequency of the excitation is set to 488.3 Hz and the highest harmonic used is the 35th. This bandlimited signal is sampled and averaged over a few hundred cycles in the time domain. The frequency domain representation of the data is obtained by employing fast Fourier transform algorithms. The phase delay and the modulation ratio of each sampled harmonic are then computed. At least four log-spaced harmonic phases or modulations are averaged before decoding the two lifetimes of temperature and oxygen phosphorescent sensors. A component of zero lifetime is introduced to account for the excitation backscatter leakage through optical interference filters seen by the photodetector. Linear and second-order empirical polynomials are employed to compute the temperatures and oxygen concentrations from the inverse lifetimes. In the situation of constant oxygen concentration, the lifetime of Pt(TPP) changes with temperature but can be compensated using the measured temperature lifetime. The system drift is 0.24 degree C for the temperature measurement and 0.59% for the oxygen concentration measurement over 30 h of continuous operation. The instrumentation and methods allow for 6-s update times and 90-s full-response times.

Algorithms↗

Optical coherence tomography for optical biopsy. Properties and demonstration of vascular pathology.

BACKGROUND: Optical coherence tomography (OCT) is an recently developed medical diagnostic technology that uses back-reflected infrared light to perform in situ micron scale tomographic imaging. In this work, we investigate the ability of OCT to perform micron scale tomographic imaging of the internal microstructure of in vitro atherosclerotic plaques. METHODS AND RESULTS: Aorta and relevant nonvascular tissue were obtained at autopsy. Two-dimensional cross-sectional imaging of the exposed surface of the arterial segments was performed in vitro with OCT. A 1300-nm wavelength, superluminescent diode light source was used that allows an axial spatial resolution of 20 microns. The signal-to-noise ratio was 109 dB. Images were displayed in gray scale or false color, Imaging was performed over 1.5 mm into heavily calcified tissue, and a high contrast was noted between lipid- and water-based constituents, making OCT attractive for intracoronary imaging. The 20-microns axial resolution of OCT allowed small structural details such as the width of intimal caps and the presence of fissures to be determined. The extent of lipid collections, which had a low backscattering intensity, also were well documented. CONCLUSIONS: OCT represents a promising new technology for imaging vascular microstructure with a level of resolution not previously achieved with the use of other imaging modalities. It does not required direct contact with the vessel wall and can be performed with a catheter integrated with a relatively inexpensive optical fiber. The high contrast among tissue constituents, high resolution, and ability to penetrate heavily calcified tissue make OCT an attractive new imaging technology for intracoronary diagnostics.

Arteriosclerosis↗

Optical coherence tomography of the human retina.

OBJECTIVE: To demonstrate optical coherence tomography for high-resolution, noninvasive imaging of the human retina. Optical coherence tomography is a new imaging technique analogous to ultrasound B scan that can provide cross-sectional images of the retina with micrometer-scale resolution. DESIGN: Survey optical coherence tomographic examination of the retina, including the macula and optic nerve head in normal human subjects. SETTING: Research laboratory. PARTICIPANTS: Convenience sample of normal human subjects. MAIN OUTCOME MEASURES: Correlation of optical coherence retinal tomographs with known normal retinal anatomy. RESULTS: Optical coherence tomographs can discriminate the cross-sectional morphologic features of the fovea and optic disc, the layered structure of the retina, and normal anatomic variations in retinal and retinal nerve fiber layer thicknesses with 10-microns depth resolution. CONCLUSION: Optical coherence tomography is a potentially useful technique for high depth resolution, cross-sectional examination of the fundus.

Fovea Centralis↗

Quantification of nerve fiber layer thickness in normal and glaucomatous eyes using optical coherence tomography.

PURPOSE: Quantitative assessment of nerve fiber layer (NFL) thickness in normal and glaucomatous eyes, and correlation with conventional measurements of the optic nerve structure and function. METHODS: We studied 59 eyes of 33 subjects by conventional ophthalmologic physical examination, Humphrey 24-2 visual fields, stereoscopic optic nerve head photography, and optical coherence tomography. RESULTS: Nerve fiber layer thickness as measured by optical coherence tomography demonstrated a high degree of correlation with functional status of the optic nerve, as measured by visual field examination (P = .0001). Neither cupping of the optic nerve nor neuroretinal rim area were as strongly associated with visual field loss as was NFL thickness (P = .17 and P = .21, respectively). Cupping correlated with NFL thickness only when the cup was small (cup-to-diameter ratio, 0.1 to 0.3) or large (cup-to-diameter ratio, 0.8 to 1.0) (P = .006); there was no correlation between cupping and NFL thickness otherwise. Nerve fiber layer, especially in the inferior quadrant, was significantly thinner in glaucomatous eyes than in normal eyes (P = .04). Finally, we found a decrease in NFL thickness with aging, even when controlling for factors associated with the diagnosis of glaucoma (P = .03). CONCLUSIONS: Nerve fiber layer thickness can be measured using optical coherence tomography. These measurements provide good structural and functional correlation with known parameters.

Female↗

Imaging of macular diseases with optical coherence tomography.

BACKGROUND/PURPOSE: To assess the potential of a new diagnostic technique called optical coherence tomography for imaging macular disease. Optical coherence tomography is a novel noninvasive, noncontact imaging modality which produces high depth resolution (10 microns) cross-sectional tomographs of ocular tissue. It is analogous to ultrasound, except that optical rather than acoustic reflectivity is measured. METHODS: Optical coherence tomography images of the macula were obtained in 51 eyes of 44 patients with selected macular diseases. Imaging is performed in a manner compatible with slit-lamp indirect biomicroscopy so that high-resolution optical tomography may be accomplished simultaneously with normal ophthalmic examination. The time-of-flight delay of light backscattered from different layers in the retina is determined using low-coherence interferometry. Cross-sectional tomographs of the retina profiling optical reflectivity versus distance into the tissue are obtained in 2.5 seconds and with a longitudinal resolution of 10 microns. RESULTS: Correlation of fundus examination and fluorescein angiography with optical coherence tomography tomographs was demonstrated in 12 eyes with the following pathologies: full- and partial-thickness macular hole, epiretinal membrane, macular edema, intraretinal exudate, idiopathic central serous chorioretinopathy, and detachments of the pigment epithelium and neurosensory retina. CONCLUSION: Optical coherence tomography is potentially a powerful tool for detecting and monitoring a variety of macular diseases, including macular edema, macular holes, and detachments of the neurosensory retina and pigment epithelium.

Adult↗

Micrometer-scale resolution imaging of the anterior eye in vivo with optical coherence tomography.

OBJECTIVE: To demonstrate a new diagnostic technique, optical coherence tomography, for high-resolution cross-sectional imaging of structures in the anterior segment of the human eye in vivo. Optical coherence tomography is a new, noninvasive, noncontact optical imaging modality that has spatial resolution superior to that of conventional clinical ultrasonography (< 20 microns) and high sensitivity (dynamic range, > 90 dB). DESIGN: Survey of intraocular structure and dimension measurements. SETTING: Laboratory. PATIENTS: Convenience sample. MAIN OUTCOME MEASURES: Correlation with range of accepted normal intraocular structure profiles and dimensions. RESULTS: Direct in vivo measurements with micrometer-scale resolution were performed of corneal thickness and surface profile (including visualization of the corneal epithelium), anterior chamber depth and angle, and iris thickness and surface profile. Dense nuclear cataracts were successfully imaged through their full thickness in a cold cataract model in calf eyes in vitro. CONCLUSIONS: Optical coherence tomography has potential as a diagnostic tool for applications in noncontact biometry, anterior chamber angle assessment, identification and monitoring of intraocular masses and tumors, and elucidation of abnormalities of the cornea, iris, and crystalline lens.

Anterior Chamber↗

Wavelength dependence of pulsed laser ablation of calcified tissue.

Pulsed laser ablation of calcified biological tissue was studied at several wavelengths in the near-ultraviolet, visible, near- and mid-infrared regions of the spectrum. The primary tissue model was bovine shank bone, while human arterial calcified plaque and normal human artery wall were also studied at selected wavelengths for comparison. Laser irradiances were on the order of MW/mm2, fluences ranged up to 1000 mJ/mm2, and repetition rates varied between 0.3-10 Hz. Spot sizes on the tissue surface ranged from 150 to 850 microns. Laser craters made with wavelengths between lambda = 295 nm and lambda = 375 nm and in the lambda = 3 microns region exhibited the highest quality ablation with clean, sharp cuts following closely the spatial contour of the incident beam. Craters drilled with visible wavelengths between lambda = 450 nm and lambda = 590 nm were generally larger than the incident laser beam spot, irregular in shape and often surrounded by large flakes of tissue debris. Ablation fluence thresholds increased with wavelength through the visible wavelengths and into the mid-infrared, but dropped to their lowest values near lambda = 3 microns. Fluence thresholds obtained with the tissue under a 1 mm depth of saline were approximately twice air thresholds. Ablation yields also varied with wavelength, probably due to increased scattering in the visible region, and were the same under saline as in air.

Absorption↗